Aging Mice Show a Decreasing Correlation of Gene Expression within Genetic Modules 英文参考文献.docVIP

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Aging Mice Show a Decreasing Correlation of Gene Expression within Genetic Modules 英文参考文献.doc

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Aging Mice Show a Decreasing Correlation of Gene Expression within Genetic Modules 英文参考文献

AgingMiceShowaDecreasingCorrelationofGene ExpressionwithinGeneticModules LucindaK.Southworth1,ArtB.Owen2,StuartK.Kim3* 1BiomedicalInformatics,StanfordUniversity,Stanford,California,UnitedStatesofAmerica,2Statistics,StanfordUniversity,Stanford,California,UnitedStatesofAmerica, 3DevelopmentalBiology,StanfordUniversity,Stanford,California,UnitedStatesofAmerica Abstract Inthisworkwepresentamethodforthedifferentialanalysisofgeneco-expressionnetworksandapplythismethodtolook for large-scale transcriptional changes in aging. We derived synonymous gene co-expression networks from AGEMAP expressiondatafor16-month-oldand24-month-oldmice.Weidentifiedanumberoffunctionalgenegroupsthatchange co-expression with age. Among these changing groups we found a trend towards declining correlation with age. In particular,weidentifiedamodular(asopposedtouniform)declineingeneralcorrelationwithage.Weidentifiedpotential transcriptionalmechanismsthatmayaidinmodularcorrelationdecline.Wefoundthatcomputationallyidentifiedtargetsof the NF-KB transcription factor decrease expression correlation with age. Finally, we found that genes that are prone to decliningco-expressiontendtobeco-locatedonthechromosome.Ourresultsconcludethatthereisamodulardeclinein co-expression with age in mice. They also indicate that factors relating to both chromosome domains and specific transcriptionfactorsmaycontributetothedecline. Citation:SouthworthLK,OwenAB,KimSK(2009)AgingMiceShowaDecreasingCorrelationofGeneExpressionwithinGeneticModules.PLoSGenet5(12): e1000776.doi:10.1371/journal.pgen.1000776 Editor:GregoryP.Copenhaver,TheUniversityofNorthCarolinaatChapelHill,UnitedStatesofAmerica ReceivedSeptember9,2009;AcceptedNovember18,2009;PublishedDecember18,2009 Copyright:?2009Southworthetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:Thisworkwassupportedbygr